Hyperornithinemia-hyperammonemia-homocitrullinuria: a rare neurometabolic disorder in two siblings.

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is an extremely rare disorder of urea cycle, with few patients reported worldwide. Despite hyperammonemia control, the long-term outcome remains poor with progressive neurological deterioration. We report the clinical, biochemical, and molecular features of two Lebanese siblings diagnosed with this disorder and followed for 8 and 15 years, respectively.

Genetic literacy among primary care physicians in a resource-constrained setting.

Background: Genetic literacy among primary healthcare providers is crucial for appropriate patient care with the advances in genetic and genomic medicine. Studies from high-income countries highlight the lack of knowledge in genetics and the need to develop curricula for continuing professional development of non-geneticists. Scarce data is available from resource-constrained countries in Middle East and North Africa.

Mitochondrial depletion syndrome type 3: the Lebanese variant.

Mitochondrial DNA depletion syndrome type 3 is an emerging disorder linked to variants in the deoxyguanosine kinase gene, which encodes for mitochondrial maintenance. This autosomal recessive disorder is frequent in the Middle East and North Africa. Diagnosis is often delayed due to the non-specificity of clinical presentation with cerebro-hepatic deterioration.

Challenges of genetic diagnosis of inborn errors of metabolism in a major tertiary care center in Lebanon.

Inborn errors of metabolism are rare genetic disorders; however, these are prevalent in countries with high consanguinity rates, like Lebanon. Patients are suspected, based on a combination of clinical and biochemical features; however, the final confirmation relies on genetic testing. Using next generation sequencing, as a new genetic investigational tool, carries several challenges for the physician, the geneticist, and the families.

Diagnostic and Therapeutic Challenges of Hereditary Tyrosinemia Type 1 in Lebanon: A 12-Year Retrospective Review.

Hereditary tyrosinemia type 1 is a rare genetic disorder leading to liver cirrhosis and hepatocellular carcinoma. Few decades ago, dietary measures and ultimately liver transplant constituted the only treatment modalities. Nowadays, early diagnosis and therapy with nitisinone can reverse the clinical picture.

Kidney and Metabolic Phenotypes in Glycogen Storage Disease Type-I Patients.

A retrospective chart review of 32 GSD- I patients, followed at the American University of Beirut Medical Center, between 2007 and 2018 was conducted. Diagnosis was confirmed by enzymatic and/or genetic studies. Clinical presentation, growth, and kidney outcome were assessed.

Diagnosis and management of symptomatic profound biotinidase deficiency in a tertiary care center in Lebanon.

Neonatal screening for biotinidase deficiency is still lacking in several countries worldwide, although this neurocutaneous disorder is treatable and preventable. Therefore, unscreened patients are diagnosed when symptomatic; treatment with Biotin is known to reverse cutaneous symptoms and improve neurological outcome. We describe a series of five symptomatic patients diagnosed with profound biotinidase deficiency and followed at a tertiary care center in Lebanon, for a variable period from 16 months to 11 years.

Outcome of Nonketotic Hyperglycinemia in Lebanon: 14-Year Retrospective Review.

Nonketotic hyperglycinemia is a rare inborn error of glycine metabolism characterized by a severe metabolic encephalopathy with drug-resistant seizures. Here, we report the outcome of nonketotic hyperglycinemia in a cohort of patients diagnosed and followed-up at a tertiary care reference center in Lebanon, between 2000 and 2014.Eight out of 12 patients with nonketotic hyperglycinemia were retrospectively reviewed.

Pamidronate Rescue Therapy for Hypercalcemia in a Child With Williams Syndrome.

A 15-month-old male infant diagnosed with Williams Syndrome (WS) was admitted with severe hypercalcemia and nephrocalcinosis. Intravenous hydration and furosemide failed to yield an appreciable and sustainable fall in serum calcium, while the injection of pamidronate achieved a significant decrease in serum calcium in a short period of time. This bisphosphonate could be considered as a second-line treatment for refractory hypercalcemia in WS.

Treatable Genetic Metabolic Epilepsies.

In the absence of a culprit epileptogenic lesion, pharmacoresistant seizures should prompt the physician to consider potentially treatable metabolic epilepsies, especially in the presence of developmental delays. Even though the anti-seizure treatment of the epilepsies remains symptomatic and usually tailored to an electroclinical phenotype rather than to an underlying etiology, a thorough metabolic workup might reveal a disease with an etiology-specific treatment. Early diagnosis is essential in the case of treatable metabolic epilepsies allowing timely intervention.

Epileptic and electroencephalographic manifestations of guanidinoacetate-methyltransferase deficiency.

Aim: Describe the seizure-related manifestations of guanidinoacetate methyltransferase (GAMT) deficiency in two new cases and compare these to the related literature.

Methods: We reviewed the clinical and electroencephalographic manifestations of two siblings with GAMT deficiency. We also performed a thorough literature review of all cases of GAMT deficiency, using the PubMed database, and compared our findings to those previously reported.

Diagnostic challenges of aminoacidopathies and organic acidemias in a developing country: a twelve-year experience.

Background: Diagnosis of aminoacidopathies and organic acidemias constitutes a real challenge in a developing country with high consanguinity rate and no systematic newborn screening. We report a twelve-year experience with the identification of these disorders in Lebanon, based on their clinical and biochemical profiles.

Methods: In this retrospective study, we reviewed clinical presentation and biochemical investigations of 294 patients.

Spectrum of mutations in Lebanese patients with phenylalanine hydroxylase deficiency.

Phenylketonuria is an autosomal recessive inborn error of metabolism resulting from phenylalanine hydroxylase deficiency. Genetic basis of phenylalanine hydroxylase deficiency has been reported in various European and Asian countries with few reports available in Arab populations of the Mediterranean region. This is the first pilot study describing phenotype and genotype of 23 Lebanese patients with phenylketonuria.

Experience with hyperphenylalaninemia in a developing country: unusual clinical manifestations and a novel gene mutation.

We report our experience in a cohort of patients with hyperphenylalaninemia in a tertiary care referral center in Lebanon. Forty-one sequential patients were studied: 34 classical phenylketonuria (PKU), 3 hyperphenylalaninemia (non-PKU), and 4 biopterin metabolism defects. The majority of cases were clinically diagnosed at variable ages with variable neurological outcomes.

Two new familial severe infantile spasm syndromes in males.

We describe two new familial severe infantile spasm syndromes (ISSs) unrelated to Aristaless-related homeobox (ARX) gene mutation. Family A contains two male siblings each with dysmorphism, profound psychomotor delay, gastroesophageal reflux, infantile spasms, hypsarrhythmia, prominent independent central apneas, and early death. Family B contains two male siblings with dysmorphism, profound psychomotor delay, ambiguous genitalia, macular hypoplasia, neurosensory hearing deficit, gastroesophageal reflux, infantile spasms, no hypsarrhythmia, apneas, and early death in one sibling.

Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration.

We report a case of a young girl with early onset pantothenate kinase-kssociated neurodegeneration (PKAN) whose initial clinical manifestation was ataxia at the age of 2.5 years. Subsequently the patient presented to us with refractory severe dystonia resulting in essentially complete loss of motor control.

Novel mutation causing partial biotinidase deficiency in a Syrian boy with infantile spasms and retardation.

We report a case of partial biotinidase deficiency (plasma biotinidase levels: 1.30 nm/minute/mL) in a 7-month-old boy who presented with evidence of perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. His neurologic symptoms improved markedly on biotin supplementation and antiepileptic drug therapy.