A 80-year-old woman of Algerian origin was admitted to hospital for the treatment of an acute and painful fracture of the third lumbar vertebra. A computed tomography scan (CTS) was performed for this fracture and revealed a dysmorphic and enlarged liver with signs of portal hypertension (splenomegaly, collateral veins). Her past medical history was significant for obesity, vertebral osteoporosis, monoclonal gammapathy of undetermined significance (IgG kappa) and some bronchitis episodes in the past 2 years. She had neither history of liver disease nor alcohol, tobacco or illicit drug abuse. Her medical examination revealed the absence of ascites, peripheral edema, jaundice and asterixis. Laboratory tests showed abnormal liver function tests: alkaline phosphatase, 382 UI/L (reference interval, 45–117 UI/L); gamma-glutamyl-transpeptidase, 299 UI/L (reference interval, 5–55 UI/L) aspartate aminotransferase, 56 UI/L (reference interval, 15–37 UI/L); alanine aminotransferase, 25 UI/L (reference interval, 12–78 UI/L); total serum bilirubin, 0.94 mg/dL (reference interval, 0.176–1.0 mg/dL). Serum albumin was decreased, 29 g/L (reference interval, 35–50 g/L). Blood platelets count was low, 143 × 109/L (normal range, 150–400 × 109/L). INR was 1.2 and serum creatinin was 47 μmol/L. Liver stiffness measurement by transient elastography (Fibroscan®) was pathologic with an increased value of 21.3 kPa in favor of underlying cirrhosis (normal range <7–8 kPa). A gastroscopy revealed grade 2 esophageal varices with red spots which were treated by band ligation. The serological tests for viral hepatitis and autoimmune hepatitis were negative. Serum cholesterol, triglycerides, ceruloplasmin and ferritin levels were normal.\nProtein serum electrophoresis (Capillarys®, Sebia) revealed a marked decrease of the α1-globulin fraction strongly suggesting an A1AT deficiency. The low serum A1AT level determined by immuno-nephelometry (0.34 g/L, reference interval: 1.0–1.8 g/L) and the isoelectric pattern with faint bands slightly more cathodal than M2 bands were very suggestive of a Pi Mmalton allele at the homozygous state. To confirm this diagnosis, we performed the Sanger DNA sequencing of the entire SERPINA1 gene with the ABI Prism 3130XL (Applied) as previously described []. Sequence analysis (Fig. ) revealed the presence, at the homozygous state, of a deletion of the three nucleotides TTC in codon 52 (exon 2) corresponding to the Mmalton allele (HGVS nomenclature: SERPINA1:c.154_156del; p. Phe52del). This deletion was on a M2 background since it was associated with the homozygous c.374G > A and c.1200A > C single nucleotide polymorphisms, thus defining the Pi Mmalton allele (the Phe52deletion on a M1 background has been called Pi Palermo). A percutaneous liver biopsy revealed micronodular cirrhosis, without steatosis but with periodic acid-Schiff (PAS)-positive acidophilic, diastase-resistant bodies in the cytoplasm of the hepatocytes. Immunohistochemical staining using a monoclonal antibody to A1AT was positive (Fig. ). According to Child-Pugh classification and MELD score, the cirrhosis was Child-Pugh B7, MELD 9. With regards to the lung, a thoracic CT scan revealed few lesions of bronchiectasis but without lesions of emphysema and the pulmonary function tests were within the normal range.
We present a case of a 64 year old male, former smoker of 15 pack-years with past medical history of malaria and obesity, admitted at outpatient clinic for suspicion of chronic liver disease and hemochromatosis. A diagnosis of cirrhosis (Child-Pugh B7 and MELD-Na 14, and signs of hypertensive gastropathy) was established.\nAlthough there was a known alcohol consumption of approximately 90gr/alcohol/day, an extended etiological study was preformed, identifying an AAT value of 70,9 mg/dL (nephelometry), and an iron overload (total iron [Fe] of 204ug/dL; ferritin of 1078ng/ml and transferrin saturation of 99%), without primary hemochromatosis (heterozigosity for the H63D gene). Immune, copper and virology tests were negative.\nSimultaneously, the patient complained of fatigue, cough and exertion dyspnoea, without relevant findings on physical examination. Further investigation revealed a pattern of probable UIP and no emphysema in high-resolution computed tomography (HRCT) (). Bronchoscopy was unremarkable, with no microbiological agents identified, and a bronchoalveolar lavage (BAL) showing increased cellularity, with 94,0% macrophages, 5,0% lymphocytes, 1,0% neutrophils, and 0% mast cells and eosinophils. Lung function tests (LFT) were normal [post-BD FEV1/FVC 87,8; post-BD FEV1 98,4%pred; post-BD FVC 87,1%pred; TLC 89,7%pred and RV 113,9%pred], except for a moderately decreased diffusing capacity for CO (DLCO) [49% predicted]. Arterial blood gas showed hypoxemia of 68mmHg and the six-minute walking test showed a 10% decrease in peripheral oxygen saturation. No occupational risk exposures were described, and autoantibodies screening and rheumatologic evaluation were negative.\nMultiplex polymerase chain reaction combined with restriction fragment length polymorphism () detected a heterozygous MPalermo allele (M1MPalermo).\nDuring the investigation, the patient presented hyperglycaemias above 200mg/dL and a glycated haemoglobin of 13.6%, hence diagnosing type-2 diabetes mellitus.\nThus the final diagnoses of concomitant type-2 diabetes, alcoholic and AATD cirrhosis, secondary iron overload, and idiopathic pulmonary fibrosis (IPF) were established. For the first, blood glucose control was achieved with long-acting insulin, for the second, alcohol abstinence was implemented, and for the latter pirfenidone was started as well as portable oxygen concentrator.\nThe patient’s two daughters were tested, showing normal AAT levels.\nAt 6-months the patient remains stable, without hospital or emergency admissions.