cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.

We report the first, and so far, only index patient with neonatal onset MoCD type A who was diagnosed and treated early enough with cPMP to avoid severe brain injury and disability. The child presented with hypoglycemia at the age of 10 h and was diagnosed because of the incidental finding of severely decreased L-cystine in plasma. Due to a high level of awareness and excellent co-operation between metabolic laboratory and clinical services, cPMP substitution could be initiated before severe encephalopathy set in, and the child subsequently had a normal motor development.

Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.

The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency.

Purpose: Mitochondrial DNA (mtDNA) depletion syndrome (MDDS) encompasses a group of genetic disorders of mtDNA maintenance. Mutation of RRM2B is an uncommon cause of infantile-onset encephalomyopathic MDDS. Here we describe the natural history of this disease.

Monocarboxylate transporter 1 deficiency and ketone utilization.

Ketoacidosis is a potentially lethal condition caused by the imbalance between hepatic production and extrahepatic utilization of ketone bodies. We performed exome sequencing in a patient with recurrent, severe ketoacidosis and identified a homozygous frameshift mutation in the gene encoding monocarboxylate transporter 1 (SLC16A1, also called MCT1). Genetic analysis in 96 patients suspected of having ketolytic defects yielded seven additional inactivating mutations in MCT1, both homozygous and heterozygous.

Riboflavin-responsive trimethylaminuria in a patient with homocystinuria on betaine therapy.

A 17-year-old female patient with pyridoxine non-responsive homocystinuria, treated with 20 g of betaine per day, developed a strong body odour, which was described as fish-like. Urinary trimethylamine (TMA) was measured and found to be markedly increased. DNA mutation analysis revealed homozygosity for a common allelic variant in the gene coding for the TMA oxidising enzyme FMO3.

Unilateral periventricular leukomalacia in association with pyruvate dehydrogenase deficiency.

Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. A deficiency of PDH E1 alpha, a subunit of the PDH complex, is a prominent cause of congenital lactic acidosis. We describe a female infant born at term and delivered by emergency Caesarean section because of fetal distress.

The use of MR imaging and spectroscopy of the brain in children investigated for developmental delay: what is the most appropriate imaging strategy?

Objectives: Developmental delay is a common problem in paediatric practice and many children with developmental delay are referred for MR imaging. Our study was performed as part of a continuing audit process to optimise our MR protocol and case selection.

Materials And Methods: We performed MR imaging and spectroscopy protocol on 157 children with developmental delay.

Glycogen storage disease type IX: High variability in clinical phenotype.

Glycogen storage disease type IX (GSD type IX) results from a deficiency of hepatic phosphorylase kinase activity. The phosphorylase kinase holoenzyme is made up of four copies of each of four subunits (alpha, beta, gamma and delta). The liver isoforms of the alpha-, beta- and gamma-subunits are encoded by PHKA2, PHKB and PHKG2, respectively.

Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway.

We present the first two identified cases of phosphoserine aminotransferase deficiency. This disorder of serine biosynthesis has been identified in two siblings who showed low concentrations of serine and glycine in plasma and cerebrospinal fluid. Clinically, the index patient presented with intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation and died at age 7 mo despite supplementation with serine (500 mg/kg/d) and glycine (200 mg/kg/d) from age 11 wk.

Magnetic resonance spectroscopy changes following haemopoietic stem cell transplantation in children with cerebral adrenoleukodystrophy.

X-linked cerebral adrenoleukodystrophy is an aggressive, rapidly progressive disorder resulting in considerable morbidity and, left untreated, mortality. Patients typically present before the age of 10 years with progressive symptomatology including ataxia, spasticity, and focal neurological deficits. Current therapeutic options are limited, the treatment of choice being haemopoietic stem cell transplantation (HSCT).

Acute bilateral striatal necrosis with rotavirus gastroenteritis and inborn metabolic predisposition.

We present a 9-month-old male with acute rotavirus gastroenteritis who developed an acute encephalopathy with focal seizures and developmental regression. Magnetic resonance imaging showed bilateral striatal necrosis and raised glutarylcarnitine levels on tandem mass spectrometry of a (crisis) blood spot, and chromatography of organic acids revealed increased urinary excretion of dicarboxylic acid. Skin biopsy demonstrated a partial decrease in glutaryl-CoA dehydrogenase activity.

Massive subdural haematomas in Menkes disease mimicking shaken baby syndrome.

Introduction: Menkes disease is an X-linked inherited disorder of intestinal copper absorption resulting in copper deficiency. Cardinal features include hair abnormalities, facial dysmorphism, severe neurological impairment, hypothermia, arterial anomalies, bone abnormalities and a fatal outcome.

Case Report: We present a case of Menkes disease complicated by progressive macrocephaly following the development of massive subdural haematomas.