Glutaric aciduria type 1: Diagnosis, clinical features and long-term outcome in a large cohort of 34 Irish patients.

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. Adherence to strict dietary restriction, in particular a diet low in lysine, carnitine supplementation and emergency treatment in pre-symptomatic patients diagnosed by high-risk screen (HRS) or newborn screen (NBS) leads to a favourable outcome. We present biochemical and clinical characteristics and long-term outcome data of 34 Irish patients with GA1 aged 1-40 years.

Multidisciplinary Care of Patients with Inherited Metabolic Diseases and Epilepsy: Current Perspectives.

More than 650 inherited metabolic diseases may present with epilepsy or seizures. These diseases are often multisystem, life-long and induce complex needs of patients and families. Multidisciplinary care involves all stages of disease management: diagnostics, specific or symptomatic, acute and chronic treatments, and integrated care that takes into account not only medical, but also manifold psychosocial, educational, vocational and other needs of patients and their caregivers.

Secondary Hyperparathyroidism in Children with Mucolipidosis Type II (I-Cell Disease): Irish Experience.

Mucolipidosis type II (ML II) is an autosomal recessive lysosomal targeting disorder that may present with features of hyperparathyroidism. The aim of this study was to describe in detail the clinical cases of ML II presenting to a tertiary referral centre with biochemical and/or radiological features of hyperparathyroidism. There were twenty-three children diagnosed with ML II in the Republic of Ireland from July 1998 to July 2021 inclusive (a 23-year period).

The challenges of pregnancy management in pyridoxine nonresponsive homocystinuria: The Irish experience.

Many patients with inborn errors of metabolism, due to early diagnosis and improved management, are living longer with less disease burden. Several are now having families of their own. This poses challenges both for the metabolic control of the mother and potential secondary effects on the fetus, as well as the risk of inheriting the inborn error.

Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland.

Since 1972, 18 patients (10 females/8 males) have been detected by newborn bloodspot screening (NBS) with neonatal-onset maple syrup urine disease (MSUD) in Ireland. Patients were stratified into three clusters according to clinical outcome at the time of data collection, including developmental, clinical, and IQ data. A fourth cluster comprised of two early childhood deaths; a third patient died as an adult.

Plasma methionine concentrations and incidence of hypermethioninemic encephalopathy during infancy in a large cohort of 36 patients with classical homocystinuria in the Republic of Ireland.

Background: Classical homocystinuria is an autosomal recessive disorder caused by profound cystathionine β-synthase deficiency. Its biochemical hallmarks are high concentrations of plasma homocyst(e)ine and methionine. Clinical manifestations include lens dislocation, developmental delay, skeletal anomalies, or thromboembolism.

Finger Prick to Finger Tip: Use of Mobile Phone Technology to Send PKU Blood Results.

The Metabolic Dietetic Team in the National Centre for Inherited Metabolic Disorders (NCIMD) in Ireland deals with approximately 120 weekly phenylalanine (Phe) levels for both adults and children. A review of 500 Phe levels highlighted that 52% of the results were within the target range. Collaboration between information and communication technologies (ICT) departments, metabolic laboratory, and metabolic dietitians enabled the development of the PKU texting system.

Catalogue of inherited disorders found among the Irish Traveller population.

Irish Travellers are an endogamous, nomadic, ethnic minority population mostly resident on the island of Ireland with smaller populations in Europe and the USA. High levels of consanguinity result in many rare autosomal recessive disorders. Due to founder effects and endogamy, most recessive disorders are caused by specific homozygous mutations unique to this population.

Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake.

A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU). There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels.

Human heterologous liver cells transiently improve hyperammonemia and ureagenesis in individuals with severe urea cycle disorders.

Background: Urea cycle disorders (UCDs) still have a poor prognosis despite several therapeutic advancements. As liver transplantation can provide a cure, liver cell therapy (LCT) might be a new therapeutic option in these patients.

Methods: Twelve patients with severe UCDs were included in this prospective clinical trial.

RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.

Background: Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutières syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection.

The clinical, biochemical and genetic features associated with -related mitochondrial disease.

Background: Mutations in the (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

Methods: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

Beaulieu-Boycott-Innes syndrome: an intellectual disability syndrome with characteristic facies.

We report a female child from an Irish Traveller family presenting with severe intellectual disability, dysmorphic features, renal anomalies, dental caries and cyclical vomiting. Current health issues include global developmental delay, mild concentric left ventricular hypertrophy, dental malocclusion and caries and a single duplex left kidney. The proband and her mother also have multiple epiphyseal dysplasia.

Sideroblastic anaemia and primary adrenal insufficiency due to a mitochondrial respiratory chain disorder in the absence of mtDNA deletion.

A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence.

Integrin α(IIb)β₃ exists in an activated state in subjects with elevated plasma homocysteine levels.

Elevated levels of plasma homocysteine (Hcy) are an independent risk factor for cardiovascular disease and thrombosis. The molecular basis for this phenomenon is not known but may relate to modification of cell surface thiols. The platelet specific integrin α(IIb)β₃ is a cysteine-rich cell adhesion molecule that plays a critical role in platelet aggregation and adhesion in haemostasis and thrombosis.

Guanidinoacetate methyltransferase (GAMT) deficiency: late onset of movement disorder and preserved expressive language.

Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine biosynthesis, characterized by early-onset learning disability and epilepsy in most affected children. Severe expressive language delay is a constant feature even in the mildest clinical phenotypes.We report the clinical, biochemical, imaging, and treatment data of two female siblings (18y and 13y) with an unusual phenotype of GAMT deficiency.

Outcomes of siblings with classical galactosemia.

Objectives: To determine the long-term outcome of dietary intervention in siblings from 14 Irish families with classical galactosemia (McKusick 230400), an autosomal recessive disorder of carbohydrate metabolism and galactose-1-phosphate uridyltransferase (GALT) deficiency.

Study Design: Outcomes in siblings on dietary galactose restriction were studied to evaluate whether birth order (ie, time of commencement of diet) and compliance with lactose-restricted diet (galactose intake > or < 20 mg /day), assessed by dietary recall and biochemical monitoring of galactose-1-phosphate [Gal-1-P] and galactitol values, affected outcomes. The outcome variables assessed were IQ, speech, and language assessment scores, neurologic examination results, and magnetic resonance imaging (MRI) of the brain.