RESUMEN
Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation in mitochondria. Pathogenic variants in MTFMT have been described in association with clinical presentations with Leigh syndrome, as well with as multisystem involvement (particularly cardiac and ocular involvement). There is a spectrum of severity, but many reported presentations have been milder with a better prognosis than other pathogenic variants associated with Leigh syndrome. We describe the case of a 9-year-old boy homozygous for a pathogenic MTFMT variant (c.626C > T/p.Ser209Leu) who presented with hypertensive crisis on a background of hyperphagia and visual impairment. His clinical course was complicated by supraventricular tachycardia and severe autonomic instability, requiring intensive care unit admission. He also developed seizures, neurogenic bladder and bowel and had a markedly abnormal eye examination with bilateral optic atrophy. Magnetic resonance image brain showed abnormal high T2/fluid-attenuated inversion recovery signal within the dorsal brainstem and in the right globus pallidus with some reduced diffusivity. Despite recovery from the acute neurological and cardiac manifestations, he has ongoing deficits in his gross motor skills and continues to have hyperphagia with rapid weight gain (approx. 20 kg in 2 years). Ophthalmic findings are persistent. This case expands the phenotype associated with MTFMT disease.
RESUMEN
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 approximate incidence of ML II in the Republic of Ireland is, therefore, 1 per 64,000 live births. Medical records were available and were reviewed for 21 of the 23 children. Five of these had been identified as having biochemical and/or radiological features of hyperparathyroidism. Of these five, three children were born to Irish Traveller parents and two to non-Traveller Irish parents. All five children had radiological features of hyperparathyroidism (on skeletal survey), with evidence of antenatal fractures in three cases and an acute fracture in one. Four children had biochemical features of secondary hyperparathyroidism. Three children received treatment with high dose Vitamin D supplements and two who had antenatal/acute fractures were managed with minimal handling. We observed resolution of secondary hyperparathyroidism in all cases irrespective of treatment. Four of five children with ML II and hyperparathyroidism died as a result of cardiorespiratory failure at ages ranging from 10 months to 7 years. Biochemical and/or radiological evidence of hyperparathyroidism is commonly identified at presentation of ML II. Further studies are needed to establish the pathophysiology and optimal management of hyperparathyroidism in this cohort. Recognition of this association may improve diagnostic accuracy and management, facilitate family counseling and is also important for natural history data.
RESUMEN
Quantitative estimates for the global impact of COVID-19 on the diagnosis and management of patients with inborn errors of metabolism (IEM) are lacking. We collected relevant data from 16 specialized medical centers treating IEM patients in Europe, Asia and Africa. The median decline of reported IEM related services in March 1st-May 31st 2020 compared to the same period in 2019 were as high as 60-80% with a profound impact on patient management and care for this vulnerable patient group. More representative data along with outcome data and guidelines for managing IEM disorders under such extraordinary circumstances are needed.