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INTRODUCTION: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, ). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important. METHODS: Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022. RESULTS: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy. CONCLUSION: MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.
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BACKGROUND: Vitamin B12, or cobalamin (Cbl), undergoes a complex series of absorptive and intracellular processing steps before serving as a cofactor for the enzymes methylmalonyl-CoA mutase and methionine synthase. Disorders of intracellular cobalamin metabolism have variable phenotypes and age of onset related to the location of the defect in the metabolic pathway leading to a combined methylmalonic acidemia and homocystinuria (cblC, cblD, cblF and cblJ), Isolated methylmalonic acidemia (cblA, cblB and cblDv2) and isolated homocystinuria (cblDv1, cblE and cblG). OBJECTIVE AND METHODS: We conducted a retrospective study of the clinical biochemical and molecular features of a cohort of patients with disorders of intracellular Cbl metabolism followed in our Reference Centre of Inherited Metabolic Diseases (CR-IMD) for the last 23 years (2000-2023). RESULTS: CblC: P1 and P2, pré-newborn screening (NBS), had an early and severe presentation evolving to multiorgan failure and death. P3 was asymptomatic at NBS with an excellent evolution except for nystagmus and retinitis pigmentosa. P4 presented at 19Y with an atypical hemolytic uremic syndrome and is presently on hemodialysis. CblD: P5 had a developmental delay (DD) and hypotonia and presented at 14m with seizures. CblDv2: P6 had DD and failure to thrive (FTT) and presented at 4Y with acute metabolic acidosis. CblDv1: P7 had DD, FTT, and hypotonia and presented at 16m with seizures and anemia. CblG: P8 had DD and FTT and presented at 15m with macrocytic anemia. In all, characteristic biochemical profiles guided the diagnosis, afterward confirmed by genetic analysis (4 MMACHC, 3 MMADHC, 1 MTR). All patients received either betaine, hydroxycobalamin, or both (P3 is on a very high dosage). CONCLUSION: Our cohort of patients has similar clinical and biochemical characteristics to the ones described in the literature. Outcomes of patients reinforce the importance of newborn screening and the need for consensus guidelines for optimal doses of parenteral hydroxocobalamin.
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Primary ciliary dyskinesia is an autosomal recessive disease with a clinical history of upper and lowers respiratory infections, rhinosinusitis and bronquitis associated with complete or partial situs inversus. The authors present a 78 -year -old male caucasian patient with rhinosinusitis, lower respiratory tract infection and dyspnea, chronic otitis with hearing deficit and infertility followed in Gastroenterology for dyspepsia and constipation. The radiological studies revealed agenesis of right frontal sinus; bronchial wall thickening; bronchiectasis; cecum and ascending colon located on the left and small bowel occupies right side of abdomen. He had no immunodeficiency, allergies, cystic fibrosis and others. We concluded primary ciliary dyskinesia with heterotaxy. For the rarity of this case we decided to present it.