Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Clinical, Endocrine and Genetic spectrums of Mucopolysaccharidoses type VI in Duhok city, Kurdistan Region, Iraq.

Mucopolysaccharidoses type VI is a rare disorder and establishing the diagnosis requires assays that are unavailable in a routine care setting. There is an increased risk of considerable diagnostic delay and missing patients due to incorrect diagnosis. The present study was conducted to determine the socio-demographic characteristics, clinical manifestations, and anthropometric parameters of patients with MPS type VI. Patients' enzyme levels and genetic profiles were also examined. The present study included a total of 16 patients who had been diagnosed as MPS type VI and were referred to Hivi Pediatric Hospital in Duhok, Kurdistan Region, Iraq, till the time period of March 2022. Diagnoses were made in all the patients by analyzing the enzyme level. Moreover, a genetic study was performed to confirm the diagnosis. From each of the patients, a blood sample was taken to determine the hematological parameters. Among the study participants, 9 were males and 7 were females. The mean age of the patients was 6.81±4.99 years and the age at diagnosis was 21.13±15.19 months. All of them presented with a course facial features, 75% had short stature, 87.5% had corneal clouding, 12.5%  had glaucoma, 68.75% had poor vision, 18.75% of them had optic nerve disease, 56.25% had otitis media, 56.25% had poor hearing, 68.75% had a history of recurrent sinusitis, 50% had an enlarged tongue, and 75% had abnormal teeth. Approximately 56.25% of the patients presented with sleep apnea, 37.5% had obstructive and restrictive airway disease, none of the patients had cardiac arrhythmia, 37.5% had cardiomyopathy, 31.25% had abdominal hepatosplenomegaly, 81.25% had skeletal abnormalities, all of the patients had normal intelligence, 9 (56.25%) had a past medical history of other systemic illness and 7 (43.75%) had a past history of surgery. Out of the total number of patients, 13 patients had c.962T>C (p.(Leu321Pro)) mutation, one patient had c.585T>A (p.(ASP195Glu)) mutation, one patient had c.[585T>A];[753C>G] (Asp195 Glu];[Tyr251 Ter]), and one patient had c.{288C>A];[962T>C]   (p.[Ser96Arg];[Leu321Pro]) mutations. Due to the rarity in prevalence, early detection of the said disorder is critical; early treatment may result in improved outcomes, which may have potential significance for newborn screening.